Ornithine Aminotransferase Deficiency in Gyrate Atrophy: Our goal is to isolate a molecular probe for the human ornithine aminotransferase (OAT) in the form of a cDNA molecule and to use it to investigate the nature of the OAT gene defect(s) present in gyrate atrophy patients. We have employed the expression cloning vector system, Lambdagt11 for cDNA cloning; clones can be isolated from a Lambdagt11 cDNA library by the Western screening method using a specific antibody directed against the protein product of the gene desired. Messenger RNAs (mRNAs) were prepared from human liver, retina, and retinoblastoma cells. Lambdagt11 cDNA libraries were made with all three mRNA populations, and the libraries were screened by the Western method using the prepared anti-OAT antibodies. A putative OAT cDNA clone was isloated from the retinoblastoma cDNA library which gives positive reactions with anti-OAT antibodies from two different sources. Hereditary Retinoblastoma: We have begun to investigate the molecular basis of malignant transformation in hereditary retinoblastoma using cell culture and molecular genetic techniques. In order to test for the presence of "activated" oncogene(s) in retinoblastoma, we have transfected the chromosomal DNA of retinoblastoma cells (Y79) on various types of cells in culture. The transfections on NIH 3T3, CV-l, and newborn mouse retinal cells have not yielded any transformed cell phenotype. In view of the published data indicating that induction of hereditary retinoblastoma may involve a loss of inactivation of a gene on chromosome 13, we are also investigating the possibility that the genomic DNA from normal human retina, when transfected on retinoblastoma cells, may be able to change the phenotype of retinoblastoma to that of a more "normal" cell. To determine if retinoblastoma has a dominant or recessive malignant phenotype, retinoblastoma cells are being fused with normal cells, and the growth characteristics of the hybrid cells are being studied.